AIDS is characterized by infection with HIV which leads to collapse of the immune system. Although highly active antiretroviral therapy (HAART) has contributed significantly to lowering morbidity and mortality from AIDS, antiretroviral drugs do not fully restore the immune system and patients often fail multi-drug treatment. Hence, there is a need for alternative/complementary medicine (CAM) that can restore an immune system ravaged by HIV/AIDS. To address this need, investigators have formed a multidisciplinary collaboration to evaluate and demonstrate utility of natural immune-based modulators in ethnically diverse patients with HIV/AIDS. The long-term goal of this proposal is to develop a CAM therapy to facilitate immune reconstitution and HIV eradication following cessation of antiretroviral treatment or concurrent with continued antiretroviral treatment. It is based on the premise of a widespread deficiency of glutathione (GSH), vital to lymphocyte function, in patients with HIV/AIDS. The proposed project will study the immunomodulatory and antiretroviral effects of a dietary antioxidant, alpha-lipoic acid (ALA), which is known to efficiently boost systemic GSH. In this amended placebo-controlled study, 42 HIV-infected adults unresponsive to HAART (i.e. those with persistent CD4+ count <50 cells/mm3, viral load> 10,000 copies/cc) will be randomized into two arms, treatment and control, of 21 patients each. The treatment group will be given 300 mg ALA thrice daily for 6 months and the control group will receive inert placebo. Studies performed at baseline, bimonthly and at 6 months will include estimation of CD4+ count, HIV RNA, T-cell reactivity in vitro and whole blood GSH level. Significance of changes from baseline parameters will be analyzed by unpaired t-tests. The proposed research will show whether GSH augmentation by ALA increases CD4+ cell number and T cell function and reduces viral load in subjects unresponsive to antiretroviral therapy.